ArticlePloS one2010
Establishment of a mouse model with misregulated chromosome condensation due to defective Mcph1 function.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 52 citations in OpenAlex.
- Review
- Neurogenesis in primates versus rodents and the value of non-human primate models.National science review · 2023Review
- DNA damage and repair: underlying mechanisms leading to microcephaly.Frontiers in cell and developmental biology · 2023Review
- Emerging roles of centrosome cohesion.Open biology · 2022Review
- The Central Domain of MCPH1 Controls Development of the Cerebral Cortex and Gonads in Mice.Cells · 2022Article
- Review
- Multifaceted Microcephaly-Related Gene MCPH1.Cells · 2022Review
- Identification of Pathogenic Mutations in Primary Microcephaly- (MCPH-) Related Three GenesBioMed research international · 2022Article
- The N-terminal BRCT domain determines MCPH1 function in brain development and fertility.Cell death & disease · 2021Article
- Autosomal Recessive Primary Microcephaly: Not Just a Small Brain.Frontiers in cell and developmental biology · 2021Review
- Microcephalin 1/BRIT1-TRF2 interaction promotes telomere replication and repair, linking telomere dysfunction to primary microcephaly.Nature communications · 2020Article
- Novel compound heterozygous mutations in MCPH1 gene causes primary microcephaly in Saudi family.Neurosciences (Riyadh, Saudi Arabia) · 2018Article
- Overexpression of MCPH1 inhibits the migration and invasion of lung cancer cells.OncoTargets and therapy · 2018Article
- Copb2 is essential for embryogenesis and hypomorphic mutations cause human microcephaly.Human molecular genetics · 2017Article
- MCPH1, mutated in primary microcephaly, is required for efficient chromosome alignment during mitosis.Scientific reports · 2017Article
- TALEN-based generation of a cynomolgus monkey disease model for human microcephaly.Cell research · 2016Article
- CEP63 deficiency promotes p53-dependent microcephaly and reveals a role for the centrosome in meiotic recombination.Nature communications · 2015Article
- The centrosome and its duplication cycle.Cold Spring Harbor perspectives in biology · 2015Review
- Homozygous loss of DIAPH1 is a novel cause of microcephaly in humans.European journal of human genetics : EJHG · 2015Article
- Molecular genetics of human primary microcephaly: an overview.BMC medical genomics · 2015Review
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Authors and funding
21 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the human gene MCPH1 cause primary microcephaly associated with a unique cellular phenotype with premature chromosome condensation (PCC) in early G2 phase and delayed decondensation post-mitosis (PCC syndrome). The gene encodes the BRCT-domain containing protein microcephalin/BRIT1. Apart from its role in the regulation of chromosome condensation, the protein is involved in the cellular response to DNA damage. We report here on the first mouse model of impaired Mcph1-function. The model was established based on an embryonic stem cell line from BayGenomics (RR0608) containing a gene trap in intron 12 of the Mcph1 gene deleting the C-terminal BRCT-domain of the protein. Although residual wild type allele can be detected by quantitative real-time PCR cell cultures generated from mouse tissues bearing the homozygous gene trap mutation display the cellular phenotype of misregulated chromosome condensation that is characteristic for the human disorder, confirming defective Mcph1 function due to the gene trap mutation. While surprisingly the DNA damage response (formation of repair foci, chromosomal breakage, and G2/M checkpoint function after irradiation) appears to be largely normal in cell cultures derived from Mcph1(gt/gt) mice, the overall survival rates of the Mcph1(gt/gt) animals are significantly reduced compared to wild type and heterozygous mice. However, we could not detect clear signs of premature malignant disease development due to the perturbed Mcph1 function. Moreover, the animals show no obvious physical phenotype and no reduced fertility. Body and brain size are within the range of wild type controls. Gene expression on RNA and protein level did not reveal any specific pattern of differentially regulated genes. To the best of our knowledge this represents the first mammalian transgenic model displaying a defect in mitotic chromosome condensation and is also the first mouse model for impaired Mcph1-function.
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